COVID‐19 and the increase in schizophrenia incidence in the future: A hypothesis and a serious warning

Abstract Background and Aims The coronavirus disease 2019 (COVID‐19), which has caused a global pandemic, is brought on by the Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2). Since the COVID‐19 pandemic started so recently, dealing with complications that emerge years later and have the potential to cause several crises for humanity is one of the issues we face in the post‐COVID‐19 age. Therefore, we wish to discuss a theory and potential dangers surrounding the probability of schizophrenia following COVID‐19 infection in this study. Methods The literature search for this article has been entirely internet‐based. Information was gathered using the Web of Science, PubMed, Scopus, and Google Scholar databases. Results The results showed that multiple immune system changes brought on by COVID‐19 have been identified as potential causes of schizophrenia. Conclusion It is predicted that one of the long‐term effects of COVID‐19 is an increase in the risk of schizophrenia incidence based on the results of this study, which looked at the pathophysiology and etiology of schizophrenia as well as the pathogenic mechanisms of the SARS‐CoV‐2. Therefore, healthcare staff should be prepared to handle any potential risks in future.


| BACKGROUND
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the culprit behind the coronavirus disease of 2019 (COVID-19), leading to a pandemic worldwide. Globally, this pandemic has caused serious problems, and our knowledge of this disease is still developing. 1 Our understanding of the short-and long-term complications of SARS-CoV-2 infection is continuously expanding as our experience with this virus evolves. Various studies have reported neurological and neuropsychiatric complications in patients with COVID-19. 2,3 Considering that not much time has passed since the start of the COVID-19 pandemic and also that this disease is mysterious, one of the challenges we face in the post-COVID-19 era is to meet the complications that manifest themselves years later and it may cause many crises for humanity. Therefore, in this study, we want to propose a hypothesis and possible threats about the possibility of schizophrenia incidence following COVID-19 infection so that health activists around the world can prevent possible risks by working on this issue and being ready to face the possible dangers.

| Etiology
The etiology of schizophrenia has not been clearly defined. According to several studies, alterations in numerous neurotransmitters, such as glutaminergic and GABA hypoactivity or dopaminergic, serotonergic, and alpha-adrenergic hyperactivity, contribute to the development of schizophrenia. Genetics also has a substantial impact. 7 One of the causes of schizophrenia may be inflammatory changes and an imbalance of cytokines. 8 Research on the etiology of schizophrenia has long focused on infection and immunity. Numerous studies have discovered that prenatal exposure to bacterial, viral, and Toxoplasma gondii infections increases the risk of schizophrenia. 9,10 Viral infection has been identified as one of the environmental risk factors for schizophrenia in epidemiological research. 11 In those who are genetically predisposed, prenatal and perinatal infections may have an impact on the immune response or brain developmentt and lead to schizophrenia.
There is a T helper (Th) 1/Th2 imbalance in untreated schizophrenia patients, with suppressed levels of Th1-related cytokines and compensatory raised Th2-cytokine levels. The primary cell type in preserving immunological homeostasis, including the balance of the innate and adaptive immune systems, is the regulatory T cell (Treg) cell.
Tregs primarily control the neuroimmune interaction between astrocytes and microglia in the central nervous system (CNS). In schizophrenia, impaired Treg cells cause astroglial overactivation and microglial pruning. In the development of Treg cells, interleukin (IL)-2 is crucial. 12 3 | COVID-19 AND SCHIZOPHRENIA  writingreview and editing. Hedyeh Askarpour: Writingreview and editing.

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

TRANSPARENCY STATEMENT
The lead author Hedyeh Askarpour affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.